Gene/Protein Disease Symptom Drug Enzyme Compound
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Patients with end stage renal failure have elevated plasma levels of atrial natriuretic peptide (ANP) which seems to be a sensitive parameter of body fluid status. A prospective study comparing patients on hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) was still missing. Six identical patients (59 +/- 10 yrs, residual diuresis 1.3 +/- 0.61, 1 data expressed as means +/- SEM) were studied in the predialysis phase and under steady state conditions on HD and on CAPD. Plasma levels of ANP, cyclic guanosine monophosphate (cGMP), adrenaline, noradrenaline and dopamine were determined. Blood and dialysate samples were repeatedly taken. Ultrafiltration-volume, dry weight and blood pressure were not different between HD and CAPD. ANP and cGMP reached the highest plasma levels in the predialysis phase with 421 +/- 180 pg/ml and 19.8 +/- 6.4 pmol/ml and decreased after the onset of dialysis treatment. On HD mean ANP levels of 279 +/- 175 pg/ml were not significantly different from those on CAPD (320 +/- 213 pg/ml). However, cGMP concentrations on CAPD (15.7 +/- 5.4 pmol/ml) surpassed the values measured on HD (10.5 +/- 3.4 pmol/ml, p less than 0.05). Plasma noradrenaline was markedly elevated in the predialysis phase (421 +/- 180 pg/ml) and decreased under dialysis treatment. Differences between HD and CAPD were not found. Adrenaline and dopamine concentrations fell within the normal range.
Adv Perit Dial 1990
PMID:Intraindividual comparison of ANP, cGMP and plasma catecholamines between HD and CAPD. 198 11

In vitro experiments were performed to analyze problems with the determination of erythropoietin in dialysate. Human recombinant erythropoietin (EPO; 4000 U/L) was added to several fluids, to glass or polystyrene tubes with or without addition of bovine serum albumin (BSA) and to dialysate bags. The recovery in peritoneal effluent was 4120 +/- 203 U/L (mean +/- SEM). The recovery in the other fluids was less than 50% but in glass tubes it increased to 96% after addition of BSA. Binding was also found to the dialysate bag, therefore reducing the amount available for absorption. We recommend that EPO samples from the dialysate are drawn within BSA coated glass tubes.
Adv Perit Dial 1990
PMID:Accuracy of erythropoietin determination in the dialysate of CAPD patients. 198 29

Plasma phosphate values were examined in 72 renal transplant patients in a randomised trial of immunosuppression with azathioprine and prednisolone versus cyclosporin alone. From 21 to 77 days after transplantation, in patients with plasma creatinine concentrations of 75-150 mumol/l, mean plasma phosphate was 0.98 (SEM 0.04) mmol/l in cyclosporin-treated patients, compared with 0.65 (SEM 0.12) mmol/l in cyclosporin-treated patients receiving pulse methylprednisolone for rejection (P less than 0.003), and 0.68 (SEM 0.02) mmol/l in patients treated with azathioprine and prednisolone (P less than 0.001). There was no difference between the mean plasma creatinine of these groups of patients. A preliminary study by nuclear magnetic resonance spectroscopy of four patients with asymptomatic chronic hypophosphataemia showed reduced concentrations of intracellular phosphate in resting muscle, and further abnormalities developed on exercise. Thus, exogenous steroid administration is a major contributing factor of hypophosphataemia in the early post-transplant period. In addition chronic hypophosphataemia may be associated with reduced intracellular inorganic phosphate concentrations detectable by nuclear magnetic resonance spectroscopy, although these changes are not apparently associated with any clinical symptoms.
Nephrol Dial Transplant 1990
PMID:Hypophosphataemia after renal transplantation: relationship to immunosuppressive drug therapy and effects on muscle detected by 31P nuclear magnetic resonance spectroscopy. 210 86

We have investigated lactate intolerance in nine patients with acute hepatorenal failure during 21 machine haemofiltration treatments using a lactate based replacement solution. In all cases hyperlactataemia occurred, the mean arterial lactate increased from 1 +/- 0.2 mmol/l (mean +/- SEM) prior to treatment to 3.2 +/- 0.3 mmol/l at 1 h (P less than 0.01), 4.2 +/- 0.4 mmol/l at 2 h (P less than 0.01), 4.2 +/- 0.4 mmol/l at 3 h (P less than 0.01) and 3.9 +/- 0.4 mmol/l (P less than 0.01) post-treatment. There were correlations between the maximum increase in blood lactate and both the change in arterial hydrogen ion concentration (r = 0.71, P = 0.001) and the mean arterial blood pressure prior to starting treatment (r = -0.57, P = 0.007). During eight of the treatments (38%), the arterial hydrogen ion concentration increased. This group showed increased lactate intolerance in association with a lesser pretreatment mean arterial pressure. The administration of exogenous lactate to patients with hepatorenal failure who are at, or near to, the threshold of their own endogenous lactate metabolism can result in an increase in hydrogen ion concentration rather than the expected decrease, and therefore lactate-based dialysate solutions are best avoided.
Nephrol Dial Transplant 1990
PMID:Paradoxical increase in arterial hydrogen ion concentration in patients with hepatorenal failure given lactate-based fluids. 211 25

A risk of beta 2-microglobulin (beta 2-M)-associated amyloidosis in long-term CAPD patients has been recognised. We examined the kinetics of beta 2-M and potential clinical manifestations of amyloidosis in patients well-established on CAPD for 1-76 months (mean +/- SEM; 16.4 +/- 14 months). In 57 patients, serum beta 2-M concentration was elevated to 30 +/- 1.8 (mean +/- SEM, mg/l) and correlated positively with the duration on CAPD. In 18 patients studied with variable degrees of residual renal function, serum beta 2-M concentration increased with declining renal function; this was most marked when the creatinine clearance was less than 1 ml/min. Using an isosmolar solution (302 +/- 1.3 mOsm/kg) containing 5% glucose polymer (9.4 mmol/l; MW 16,800), the transperitoneal elimination of beta 2-M was significantly enhanced (1.6 times) compared to conventional 1.36% glucose solution, but without a detectable change in serum concentrations during a 6-h study. No significant difference was found between the estimated minimum volume of distribution of beta 2-M in CAPD and haemodialysis patients. Symptomatic amyloid-associated disease was absent in patients in this study, and may be attributed to the short duration of dialysis.
Nephrol Dial Transplant 1990
PMID:Kinetic and clinical studies of beta 2-microglobulin in continuous ambulatory peritoneal dialysis: influence of renal and enhanced peritoneal clearances using glucose polymer. 213 Feb 98

To evaluate the pharmacokinetics of ofloxacin, a novel quinolone antibiotic, in patients with end-stage renal disease (ESRD) on continuous ambulatory peritoneal dialysis (CAPD), we investigated 6 patients in a single-dose study and 9 patients in a multiple-dose study, all without peritonitis. In the single-dose study, patients received 200 mg ofloxacin orally. Serum concentrations (Cmax) peaked at 3.1 +/- 0.3 mg/L (mean +/- SEM), 1.6 +/- 0.5 h after p.o. administration of the drug. Elimination half-life (t1/2) was 26.8 +/- 2.5 h. Peritoneal clearance accounted for 10% of the total body clearance. After 5-h dwell time, ofloxacin concentrations in the dialysate were 1.5 +/- 0.2 mg/L, which is above the MIC90 for most bacteria responsible for peritonitis in patients on CAPD. In the multiple dose study, 200 mg ofloxacin were administered twice, with a time interval of 12 h, followed by 200 mg for 9 days every morning. Mean trough serum levels were 2.6 +/- 1.0 mg/L, mean peak concentrations were 4.1 +/- 1.7 mg/L. Mean ofloxacin concentrations in the peritoneal effluent were 1.9 +/- 0.9 mg/L. It is concluded that an oral loading dose of 400 mg on the first day and a maintenance dose of 200 mg ofloxacin/day does not lead to significant accumulation, even though the elimination by the peritoneal route is only small. The proposed dosing regimen could be an adequate therapy of peritonitis and exit-site infections in patients on CAPD since levels reached in the dialysate effluent are bactericidal. The clinical usefulness in the treatment of peritonitis has to be proven in further studies.
Perit Dial Int 1989
PMID:Single- and multiple-dose kinetics of ofloxacin in patients on continuous ambulatory peritoneal dialysis (CAPD). 248 79

The effect of pulse intravenous methylprednisolone therapy followed by oral immunosuppression was evaluated in ten patients with idiopathic membranous glomerulonephritis who had developed progressive renal failure--a group generally considered to have a poor prognosis. The patients (six male, four female, mean age 50 years) were monitored over 9-30 months during which time creatinine clearance reduced from (mean +/- SEM) 83 +/- 10 to 29 +/- 6 ml/min, and plasma creatinine increased from 135 +/- 22 to 297 +/- 35 mumol/l. All patient were nephrotic with mean 24-h urinary protein excretion ranging from 5.8 to 19.6 g. Treatment administered was pulse intravenous methyl-prednisolone 1 g X 3 then oral prednisolone 30 mg and azathioprine 50 mg (nine patients) or cyclophosphamide 50 mg (one patient). Mean prednisolone dosage was 25 mg at 3 months, 16 mg at 6, and 10 mg at 12 months. Patients have been followed up for between 12 and 57 months on therapy. Creatinine clearance increased to 39 +/- 6, 47 +/- 5 and 48 +/- 18 ml/min after 3, 6 and 12 months treatment with a fall in proteinuria to 6.2 +/- 1.7, 5.7 +/- 1.4, and 3.1 +/- 1.1 g/24h. The deterioration of renal function was reversed in six patients (associated with a reduction in proteinuria to less than 1 g/24 hours in five), slowed in three (with a significant reduction in proteinuria in two), and only one patient with more advanced renal failure before treatment progressed to end-stage failure without any retardation of the rate of deterioration or change in proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)
Nephrol Dial Transplant 1989
PMID:Immunosuppression can arrest progressive renal failure due to idiopathic membranous glomerulonephritis. 249 75

This study evaluates the use of calcium carbonate in chronic renal failure. Forty-eight patients (25 male, 23 female, mean age 54.3 years, six pre-dialysis. 12 CAPD, 30 haemodialysis) on phosphate restriction and requiring aluminum hydroxide (mean 2.4 +/- 0.8 g/day) to control serum phosphate, were converted to an equivalent dose of calcium carbonate (2.5 +/- 0.6 g/day). None received vitamin D analogues. Three months post-conversion there was a significant decrease in mean (+/- SEM) serum phosphate (1.86 +/- 0.08 versus 1.66 +/- 0.05 mmol/l P less than 0.01) and serum aluminum (28.3 +/- 5.4 versus 13.2 +/- 3.0 micrograms/l, P less than 0.0001): calcium/phosphate product was unchanged. Post-conversion there was an increase in serum bicarbonate, (20.6 +/- 0.5 versus 22.1 +/- 0.6 mmol/l, P less than 0.01) and serum calcium (2.32 +/- 0.02 versus 2.45 +/- 0.03 mmol/l, P less than 0.0001). No change in serum creatinine, alkaline phosphatase or parathormone occurred. No adverse effects were reported but nine (18%) patients became hypercalcaemic (2.7 to 2.93 mmol/l), eight of whom responded to dose reduction. Hypercalcaemia did not correlate with pre-conversion serum calcium, parathyroid hormone, alkaline phosphatase or aluminium. Calcium carbonate is an effective alternative to aluminium-based phosphate binders. It produces a beneficial increase in serum calcium and bicarbonate and a significant decrease in serum aluminium. Hypercalcaemia is unpredictable but is easily reversible in the majority of patients.
Nephrol Dial Transplant 1989
PMID:The use of calcium carbonate to treat the hyperphosphataemia of chronic renal failure. 251 82

The possible presence of lithium transport beyond the proximal tubule was examined by measuring lithium excretion after administration of triamterene, a potassium-sparing diuretic, exclusively acting in the cortical collecting tubule. Eight young and healthy volunteers were studied on two occasions during maximal water diuresis. After obtaining baseline values triamterene (100 mg orally) or placebo was administered, and measurements continued for 4 hours. Creatinine clearance was used as a marker of glomerular filtration rate, and phosphate excretion was used as an additional marker of proximal sodium transport. Compared to placebo (P), triamterene (T) caused a significant increase in fractional excretion of sodium (P, 0.74 +/- 0.08%; T, 1.73 +/- 0.24%, mean +/- SEM; P less than 0.01), and lithium (P, 21.2 +/- 1.3%; T, 27.5 +/- 1.5%; P less than 0.01), whereas fractional excretion of phosphate remained unchanged (P, 9.8 +/- 1.3%; T, 9.4 +/- 1.5%; P = NS). These results indicate that lithium is transported in the cortical collecting tubule, and provide further evidence that the use of lithium as a marker of purely proximal tubular sodium transport is of limited value.
Nephrol Dial Transplant 1989
PMID:Triamterene increases lithium excretion in healthy subjects: evidence for lithium transport in the cortical collecting tubule. 251 83

The production of the lipoxygenase metabolite of arachidonic acid, leukotriene B4 (LTB4) by normal rat glomeruli has been studied. Isolated glomeruli from saline-perfused rat kidneys were incubated in Kreb's buffer for 15 min at 37 degrees C. The concentrations of LTB4 and other eicosanoids in cell-free supernatants were determined by direct radioimmunoassays (RIA). Mean basal syntheses of eicosanoids were: thromboxane B2 (TXB2) 0.77 +/- 0.13, prostaglandin (PG) E2 0.40 +/- 0.05, 6-keto-PGF1 alpha 0.38 +/- 0.06 ng/mg glomerular protein (mean +/- SEM n = 8). In these assays immunoreactive LTB4 synthesis was 0.12 +/- 0.02 ng/mg. In samples incubated with BW755C, 50 micrograms/ml, an inhibitor of arachidonate metabolism via both the cyclo-oxygenase and lipoxygenase pathways, there was more than 80% inhibition of the synthesis of TXB2, PGE2 and 6-keto-PGF1 alpha. However, immunoreactive LTB4 was only reduced by 44%, suggesting the presence of other materials which cross-react in the RIA. The presence of authentic LTB4 in the supernatants was confirmed after extraction and high-pressure liquid chromatography (HPLC). This material represented 25% of the original material detected by RIA. Although the physiological role of LTB4 in the normal state is unknown, its chemotactic activity may be of great significance during glomerular inflammation.
Nephrol Dial Transplant 1987
PMID:Leukotriene B4 production in normal rat glomeruli. 281 88


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